Prophylactic Effect of Omega-3 Polyunsaturated Fatty Acids Monotherapy in Preventing Recurrent Major Depressive Disorder - A Randomized Controlled Trial

Sep 30, 2026

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Background: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) show efficacy as adjunctive treatment for major depressive disorder (MDD), yet fewer studies evaluate their prophylactic potential as monotherapy for preventing recurrence. A 6-month randomized controlled trial assessed whether n-3 PUFAs monotherapy reduces recurrent MDD. Sixty remitted patients were assigned to n-3 (n=30) or placebo (n=30). HRSD recurrence was defined by HRSD score >20. Results showed no monthly HRSD differences, but omega-3 monotherapy lowered recurrence at month 6 and improved survival-based recurrence prevention, with higher EPA levels but no DHA difference.

LanguageEnglish

CategoryHealthcare

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Pages11

Reading Time28 min

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Abstract

Background and Aims

Methods

Results and Conclusion

Introduction

BioMedicine | Volume 15 Issue 4 | Article 5 | | --- | --- | | 2025
Prophylactic Effect of Omega-3 Polyunsaturated Fatty Acids Monotherapy in Preventing Recurrent Major Depressive Disorder: A Randomized Controlled Trial
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This work is licensed under a Creative Commons Attribution 4.0 License. | | Recommended Citation Malau, Ikbal Andrian; Chang, Cheng-Ho; Chen, Wei-Jen; Liu, Wen-Chun; Zailani, Halliru; Liao, Hsien-Feng; Chang, Jane Pei-Chen; Chiu, Wei-Che; and Su, Kuan-Pin (2025) "Prophylactic Effect of Omega-3 Polyunsaturated Fatty Acids Monotherapy in Preventing Recurrent Major Depressive Disorder: A Randomized Controlled Trial," BioMedicine: Vol. 15 : Iss. 4 , Article 5. DOI: 10.37796/2211-8039 .1667 This Original Article is brought to you for free and open access by BioMedicine. It has been accepted for inclusion in BioMedicine by an authorized editor of BioMedicine. ORIGINAL ARTICLE Prophylactic effect of omega-3 polyunsaturated fatty acids monotherapy in preventing recurrent major depressive disorder: A randomized controlled trial Ikbal Andrian Malau a,b,1, Cheng-Ho Chang c,1, Wei-Jen Chen d,1, Wen-Chun Liu e, Halliru Zailani a,f,g, Hsien-Feng Liao h, Jane Pei-Chen Chang a,i,j, Wei-Che Chiu k,l,*, Kuan-Pin Su d,i,m,n,** a Mind-Body Interface Research Center (MBI-Lab) and Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan b Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan c Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan d An Nan Hospital, China Medical University,(CMU) Tainan, Taiwan e Department of Nursing, National Tainan Junior College of Nursing, Tainan, Taiwan f Graduate Institute of Nutrition, China Medical University, Taichung, Taiwan g Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria h Jenteh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan i College of Medicine, China Medical University,(CMU) Taichung, Taiwan j Child and Adolescent Psychiatry Division, China Medical University Hospital, Taichung, Taiwan k Department of Psychiatry, Cathay General Hospital, Taipei, Taiwan l School of Medicine, Fu Jen Catholic University, Taipei, Taiwan m Mind-Body Interface Research Center (MBI Lab & Care), CMU Hospital, Taichung, Taiwan n Ofﬁce of Research and Development, Asia University, Taichung, Taiwan Abstract Background: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have demonstrated efﬁcacy as adjunctive treatment for MDD. In fact, fewer studies assessed the prophylactic properties of n-3 PUFAs as monotherapy on the recurrence of MDD. Aims: This study aimed to assess the prophylactic effect of n-3 PUFAs monotherapy against recurrent MDD. Methods: We conducted a 6-month randomized controlled trial to assess the prophylactic effect of n-3 in preventing recurrent MDD. We assigned 60 remitted MDD patients to the n-3 group (n ¼ 30) and placebo (n ¼ 30). Furthermore, we assessed the difference in depression severity and MDD recurrence based on the 21-item Hamilton Rating Scale for Depression (HRSD) at months 1, 2, 3, 4, and 6 between groups. The recurrent event of MDD was deﬁned as an HRSD score >20. Furthermore, biochemical parameters in plasma were assessed as the secondary outcomes. Results: There was no signiﬁcant difference in the HRSD score between the n-3 group and placebo each month (pvalue >0.05). However, our ﬁndings have implicated that omega-3 monotherapy for MDD contributed to a lower recurrence rate compared to the placebo group at month 6 (p-value ¼ 0.035). Omega-3 supplementation was superior to placebo to preventing recurrent MDD analyzed using KaplaneMeier survival analysis over a 6-month study period (pvalue ¼ 0.04

FAQs

What was the study’s primary objective?

To assess the prophylactic effect of n-3 PUFAs monotherapy in preventing recurrence of major depressive disorder.

How was the trial designed and how were participants assigned?

A 6-month randomized controlled trial assigned 60 remitted MDD patients to an n-3 group (n=30) or placebo (n=30).

What did the study find about MDD recurrence and depressive severity?

There was no significant monthly difference in HRSD scores, but omega-3 monotherapy reduced recurrence at month 6 and showed superiority to placebo in survival analysis. EPA levels increased with omega-3, while DHA did not differ.

Sep 30, 2026

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